Pathogen or Bystander: Clinical Significance of Detecting Human Herpesvirus 6 in Pediatric Cerebrospinal Fluid

Abstract

Human herpesvirus 6 (HHV-6) is an important cause of meningitis and meningoencephalitis. As testing for HHV-6 in cerebrospinal fluid (CSF) is more readily available using the FilmArray Meningitis/Encephalitis panel (FA-ME; BioFire Diagnostics, Salt Lake City, UT), we aimed to determine the clinical significance of detecting HHV-6 in order to identify true infections and to ensure appropriate antiviral initiation. Chart review on 25 patients positive for HHV-6 by FA-ME was performed to determine clinical presentation, comorbidity, treatment, and outcome. The presence of chromosomally integrated HHV-6 (ciHHV-6) DNA was also investigated. Of 1,005 children tested by FA-ME, HHV-6 was detected in 25 (2.5%). Five patients were diagnosed with either HHV-6 meningitis or meningoencephalitis based on HHV-6 detection in CSF, clinical presentation, and radiographic findings. Detection of HHV-6 by FA-ME led to discontinuation of acyclovir within 12.0 h in all 12 patients empirically treated with acyclovir. Six of the 12 patients were started on ganciclovir therapy within 6.8 h; 4 of these were treated specifically for HHV-6 infection, whereas therapy was discontinued in the remaining 2 patients. CSF parameters were not generally predictive of HHV-6 positivity. The presence of ciHHV-6 was confirmed in 3 of 18 patients who could be tested. Five of the 25 patients included in the study were diagnosed with HHV-6 meningitis/meningoencephalitis. FA-ME results led to discontinuation of empirical antiviral treatment in 12 patients and appropriate initiation of ganciclovir in 4 patients. In our institution, detection of HHV-6 using FA-ME led to faster establishment of disease etiology and optimization of antimicrobial therapy.

A case presentation for positive SARS-CoV-2 RNA recurrence in a patient with a history of type 2 diabetes that had recovered from severe COVID-19

“…RT-PCR is the most useful laboratory diagnostic test for COVID-19. The first real-time RT-PCR assays targeted some parts of the RNA, such as RNA-dependent RNA polymerase, envelope and nucleocapsid genes of SARS-CoV-2 [7] . However, we do not know which part of the RNA is the key genome of SARS-CoV-2, which could decide its life cycle.…”

Human Herpesvirus 6 Associated Encephalitis with Fulminant Brain Edema in a Previously Healthy Child

“…As testing for HHV-6 in CSF is more readily available using the BIOFIRE® FilmArray® Meningitis/Encephalitis Panel, it is easier to diagnose previously undetermined etiology of encephalitis in children [5]. However, clinical significance of the finding of HHV-6 in CSF should be analyzed in the context of the patient.…”

Panels and Syndromic Testing in Clinical Microbiology

“… 28 Contrary to the 40% rate of unnecessary therapy reported, a recent study of 25 HHV-6 positive pediatric patients reported only 8% of patients (2/25) were unnecessarily treated with intravenous ganciclovir for approximately 24 hours. 29 A 20% rate of central nervous system infections was also reported, of which all had abnormal radiographic findings and the majority were immunocompetent. 29 Key tips to the interpretation of positive HHV-6 result include but are not limited to the presence of central nervous system symptoms, abnormal radiographic findings, and additional HHV-6 detection from alternate sources.…”

“… 29 A 20% rate of central nervous system infections was also reported, of which all had abnormal radiographic findings and the majority were immunocompetent. 29 Key tips to the interpretation of positive HHV-6 result include but are not limited to the presence of central nervous system symptoms, abnormal radiographic findings, and additional HHV-6 detection from alternate sources. A quantitative HHV-6 viral load of greater than 300,000 copies/mL in peripheral blood may point to chromosomal integrated HHV-6 rather than true infection, as well as consistently high HHV-6 viral load despite antiviral therapy.…”

“…A quantitative HHV-6 viral load of greater than 300,000 copies/mL in peripheral blood may point to chromosomal integrated HHV-6 rather than true infection, as well as consistently high HHV-6 viral load despite antiviral therapy. 29 Testing for chromosomal integrated HHV-6 by droplet digital PCR is available at the University of Washington.…”